Bone mineral accretion will be examined in adolescents and young adults in three related projects. For all these studies, bone mineral content (BMC) and bone mineral density (BMD) will be compared with a new expression of bone mineral, bone mineral apparent density (BMAD). BMAD normalizes BMC to a derived reference volume, thereby minimizing the effect of bone geometry and allowiing comparisons of mineral status among bones of similar shape but different size. This analysis should prove valuable in interpreting bone mineral data from the rapidly growing, healthy adolescents and the patients with unusual short stature to be included in these studies. The ethnicity and gender study will define differences in bone mineralization between healthy Caucasian, Black, Hispanic and Asian subjects ages 9-25 years. Bone mineral of the lumbar spine, whole body, and proximal femur will be determined using dual x-ray absorptiometry (DEXA) and related to age, body mass, pubertal status, calcium intake and exercise in both cross-sectional and longitudinal studies. The aim is to evaluate the sex- or gender-specific differences in bone accretion and peak bone mass and to determine other clinical correlates of bone mineral acquisition. The normative data generated by this study will aid in the interpretation of bone mineral data from children and young adults. Bone mineral will also be assessed in adolescent girls with ovarian failure using a similar protocol. Changes in bone mineral and biochemical markers of bone metabolism will be studied before and after the initiation of estrogen therapy. The goal of this project is to evaluate the independent contribution of sex steroids to adolescent bone accretion. The third study group consists of Ecuadorian patients with growth hormone-receptor deficiency (GHRD), a syndrome of severe short stature due to growth hormone resistance. This population presents a unique opportunity to assess the biologic effects of insulin-like growht factor (IGF) in vivo. Affected women with GHRD are osteopenic despite normal sexual maturation, presumably a reflection of IGF deficiency. To establish the frequency and severity of osteopenia, bone mineral density of all 46 affected patients will be compared to unaffected Ecuadorian controls. In addition, longitudinal studies of bone mineral and markers of bone turnover will be performed in all affected children as they begin longterm therapy with IGF-I. This research is directed at evaluating the independent contribution of IGF-I to bone mineral acquisition. These combined studies will further our understanding of the determinants of adolescent bone acquisition and peak bone mass which may be applied in designing preventative and therapeutic strategies in the management of osteoporosis.